He Yu, Chang Xinyue, Liu Yi, Fei Jiawen, Qin Xiaoli, Song Beiping, Yu Quan, Shi Mengyao, Guo Daoxia, Chen Jing, Wang Aili, Xu Tan, He Jiang, Zhang Yonghong, Zhu Zhengbao
Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, Jiangsu Province 215123, PR China.
Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, Jiangsu Province 215123, PR China; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
J Stroke Cerebrovasc Dis. 2025 Jan;34(1):108172. doi: 10.1016/j.jstrokecerebrovasdis.2024.108172. Epub 2024 Dec 2.
Thrombomodulin, a thrombin receptor with anticoagulant, anti-inflammatory, and cytoprotective properties, has been suggested to play a pivotal role in ischemic stroke. However, the association of plasma thrombomodulin with post-stroke cognitive impairment (PSCI) remains unclear. We aimed to prospectively investigate the associations of plasma thrombomodulin with PSCI among ischemic stroke patients in a multicenter cohort study.
We measured plasma thrombomodulin levels at baseline among 615 ischemic stroke patients from a preplanned ancillary study of the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). We used Montreal Cognitive Assessment (MoCA) to evaluate cognitive function at 3-month follow-up after ischemic stroke, and PSCI was defined as MoCA score <23.
Plasma thrombomodulin was inversely associated with PSCI, and the adjusted odds ratio of PSCI for the highest versus lowest quartile of thrombomodulin was 0.50 (95 % CI: 0.28-0.92, P=0.026). Each standard deviation increment of log-transformed thrombomodulin was associated with a 23 % (odds ratio: 0.77, 95 % CI: 0.62-0.97, P=0.029) decreased risk of PSCI. In addition, plasma thrombomodulin could significantly improve the risk reclassification of PSCI beyond established risk factors (net reclassification index: 25.04 %, 95 % CI: 7.20 %-42.87 %, P=0.007; integrated discrimination improvement: 1.13 %, 95 % CI: 0.18 %-2.09 %, P=0.020).
High plasma thrombomodulin levels were associated with a decreased risk of PSCI among ischemic stroke patients. Our findings suggest that plasma thrombomodulin might be a predictive biomarker and potential therapeutic target for PSCI.
血栓调节蛋白是一种具有抗凝、抗炎和细胞保护特性的凝血酶受体，已被认为在缺血性卒中中起关键作用。然而，血浆血栓调节蛋白与卒中后认知障碍（PSCI）之间的关联仍不清楚。我们旨在通过一项多中心队列研究，前瞻性地调查缺血性卒中患者血浆血栓调节蛋白与PSCI之间的关联。
我们在一项预先计划的CATIS（中国急性缺血性卒中降压试验）辅助研究的615例缺血性卒中患者基线时测量了血浆血栓调节蛋白水平。我们使用蒙特利尔认知评估量表（MoCA）在缺血性卒中后3个月随访时评估认知功能，PSCI定义为MoCA评分<23分。
血浆血栓调节蛋白与PSCI呈负相关，血栓调节蛋白最高四分位数与最低四分位数相比，PSCI的调整优势比为0.50（95%可信区间：0.28 - 0.92，P = 0.026）。对数转换后的血栓调节蛋白每增加一个标准差，PSCI风险降低23%（优势比：0.77，95%可信区间：0.62 - 0.97，P = 0.029）。此外，血浆血栓调节蛋白可显著改善PSCI超出既定危险因素的风险重新分类（净重新分类指数：25.04%，95%可信区间：7.20% - 42.87%，P = 0.007；综合鉴别改善：1.13%，95%可信区间：0.18% - 2.09%，P = 0.020）。
缺血性卒中患者血浆血栓调节蛋白水平高与PSCI风险降低相关。我们的研究结果表明，血浆血栓调节蛋白可能是PSCI的预测生物标志物和潜在治疗靶点。
